Alloisio Susanna, Cervetto Chiara, Passalacqua Mario, Barbieri Raffaella, Maura Guido, Nobile Mario, Marcoli Manuela
Institute of Biophysics, CNR, Via De Marini, 6 - 16149 Genoa, Italy.
FEBS Lett. 2008 Nov 26;582(28):3948-53. doi: 10.1016/j.febslet.2008.10.041. Epub 2008 Oct 31.
The presynaptic P2X7 receptor (P2X7R) plays an important role in the modulation of transmitter release. We recently demonstrated that, in nerve terminals of the adult rat cerebral cortex, P2X7R activation induced Ca2+-dependent vesicular glutamate release and significant Ca2+-independent glutamate efflux through the P2X7R itself. In the present study, we investigated the effect of the new selective P2X(7)R competitive antagonist 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine (A-438079) on cerebrocortical terminal intracellular calcium (intrasynaptosomal calcium concentration;Ca2+ signals and glutamate release, and evaluated whether P2X7R immunoreactivity was consistent with these functional tests. A-438079 inhibited functional responses. P2X7R immunoreactivity was found in about 45% of cerebrocortical terminals, including glutamatergic and non-glutamatergic terminals. This percentage was similar to that of synaptosomes showing P2X7R-mediated [Ca2+]i signals. These findings provide compelling evidence of functional presynaptic P2X7R in cortical nerve terminals.
突触前P2X7受体（P2X7R）在递质释放的调节中起重要作用。我们最近证明，在成年大鼠大脑皮层的神经末梢中，P2X7R激活可诱导Ca2+依赖性囊泡谷氨酸释放，并通过P2X7R自身诱导显著的Ca2+非依赖性谷氨酸外流。在本研究中，我们研究了新型选择性P2X(7)R竞争性拮抗剂3-(5-(2,3-二氯苯基)-1H-四氮唑-1-基)甲基吡啶（A-438079）对大脑皮层末梢细胞内钙（突触小体内钙浓度；Ca2+信号）和谷氨酸释放的影响，并评估P2X7R免疫反应性是否与这些功能测试一致。A-438079抑制功能反应。在约45%的大脑皮层末梢中发现了P2X7R免疫反应性，包括谷氨酸能和非谷氨酸能末梢。这一百分比与显示P2X7R介导的[Ca2+]i信号的突触小体的百分比相似。这些发现为皮层神经末梢中功能性突触前P2X7R提供了有力证据。
